Linked Life Data

6585203

Source:http://linkedlifedata.com/resource/pubmed/id/6585203

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1984-5-10
pubmed:abstractText
Previous work in several laboratories has shown that enzymatic reduction of nitroheterocyclic compounds to reactive but uncharacterized metabolites that damage DNA constitutes an important "activation" step in both bacteria and hypoxic mammalian cells. However, since the known mammalian enzymes having nitroreductase activity are reported to be strongly inhibited by molecular oxygen, the relation of reductive activation to the toxic and mutagenic effects of nitroheterocyclic compounds in intact animals or aerobic cultured cells is unclear. We report here that the process of net nitroreduction of 5-nitro-2-furaldehyde semicarbazone (nitrofurazone) by rat liver xanthine dehydrogenase was considerably less sensitive to inhibition by oxygen than was nitroreduction catalyzed by rat liver or milk xanthine oxidase. The dehydrogenase is the native form of xanthine oxidoreductase and is known to change to the oxidase form as liver extracts are aged or treated with various agents. Incubation at 65 degrees rapidly converted the dehydrogenase form to the oxidase form with concomitant loss of aerobic nitroreductase activity. Similarly, much of the aerobic nitroreductase activity was lost when the preparation was treated with p-hydroxymercuribenzoate but was regained upon subsequent treatment with dithiothreitol. Intermediates generated in the aerobic nitroreduction process bound tightly and probably covalently to protein. Thus, it is possible that aerobic reduction of nitrofurans and other nitroheterocyclic and nitroaromatic components by xanthine dehydrogenase may constitute a significant "activation" process which contributes to the toxic action of such agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
799-805
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1984
pubmed:articleTitle
Aerobic reduction of 5-nitro-2-furaldehyde semicarbazone by rat liver xanthine dehydrogenase.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't